Search

Ionic liquids (ILs) have attracted increasing attention since last few decades due to their high molecular design abilities and wide applications in different fields. In this study, four novel fluorescent isoquinolino [2,1-a]quinoxalin-5-ium ILs were designed and synthesized via a two-step process including a simple dual Schiff's base formation and a subsequent [RhCp∗Cl2]2-catalyzed oxidative C–H activation/annulation reaction. The as-synthesized ILs were extensively characterized using FT-IR, 1H-NMR, 13C-NMR, 19F-NMR, HSQC-NMR, HMBC-NMR and HR-MS. Their photophysical properties were determined by steady-state fluorescence spectroscopy. The results demonstrate that all these ILs showed dual or triple emissions, large stokes shift (90 nm) and mechanochromic behaviors. Basing on solvatochromism and titration experiments, it is thought that the emission bands of the ILs are raised from their local excited states, charge transfer states or excited state proton transfer of cations, while the substitute effect of these quinoxaline derived ILs on their stokes shifts is negligible.

Background: The ubiquitin-proteasome system (UPS) is critical in cellular protein degradation and widely involved in the regulations of cancer hallmarks. Targeting the UPS pathway has emerged as a promising novel treatment in hematological malignancies and solid tumors. Objective: This review mainly focuses on the preclinical results of proteasome inhibitors in solid tumors. Methods: We analyzed the published articles associated with the anticancer results of proteasome inhibitors alone or combination chemotherapy in solid tumors. Important data presented in abstract form were also discussed in this review. Results/Conclusion: Proteasome inhibitors, such as bortezomib and carfilzomib, are highly effective in treating solid tumors. The anticancer efficacy is not limited to affect the proteasomal inhibition- associated signaling pathways but also widely involves the signaling pathways related to cell cycle, apoptosis, and epithelial-mesenchymal transition (EMT). In addition, proteasome inhibitors overcome the conventional chemo-resistance of standard chemotherapeutics by inhibiting signaling pathways, such as NF-κB or PI3K/Akt. Combination chemotherapy of proteasome inhibitors and standard chemotherapeutics are widely investigated in multiple relapsed or chemo-resistant solid tumor types, such as breast cancer and pancreatic cancer. The proteasome inhibitors re-sensitize the standard chemotherapeutic regimens and induce synergistic anticancer effects. The development of novel proteasome inhibitors and delivery systems also improves the proteasome inhibitors’ anticancer efficacy in solid tumors. This review summarizes the current preclinical results of proteasome inhibitors in solid tumors and reveals the potential anticancer mechanisms.

A series of vibratile π-extended dihydrophenazines (BPs) and a tetrahydrodiphenazine (TP) were synthesized via direct C–N coupling reactions. Structural alterations of the fused acene wings lead to...

To understand the relationships between channel size and ion selectivity, we have developed a new type of artificial ion channel based on pore-forming helical polymers consisting of phenanthroline-...

Deoxynivalenol (DON) is a mycotoxin that commonly contaminates cereals worldwide. Dietary exposure to DON is a subject of great public health concern, but studies on the health effects of chronic exposure to DON are not available. In this study, we investigated the connection between DNA methylation levels and DON exposure in children. The DNA methylation status of white blood cells from 32 children aged 2~15 years old in Henan, China, was profiled. A total of 378 differentially methylated CpGs were identified between the high and low DON exposure groups, and 8 KEGG pathways were found to be significantly enriched among the differentially methylated genes. In addition, the quantitative methylation of EIF2AK4, EMID2 and GNASAS was analysed using the Sequenom MassARRAY platform. The results showed that the methylation level of EIF2AK4 was significantly different between the two groups, and the methylation levels were associated with exposure to DON. Conclusively, our study found that chronic exposure to DON during childhood could affect DNA methylation levels.

Designing a core–shell nanointerface is beneficial for enhancing the photocatalytic performance of hydrogen peroxide (H2O2) production. Hence, a direct Z-scheme one-dimensional (1 D) CuBiOS@CuBi2O4 nanorods with a core (oxide)-shell (sulfide) nanostructure and O S interpenetrated nanointerface was controllably synthesized through in-situ anion exchange. The formation of O S interpenetration at the heterogeneous interface with surface oxygen vacancies could effectively boost light absorption, reduce the interface contact resistance, facilitate band bending, and thus enhance charge separation and transfer as a “bridge”. The as-prepared catalyst with tunable O S nanointerface greatly improved the photocatalytic performances in the H2O2 production with a yield of 201.9 μmol·L-1 and the in-situ generated H2O2 effectively accelerated the reduction of chromium(VI) (Cr(VI), 95.4% within 15 min). The excellent performances were due to the O S interpenetration with rich oxygen vacancies and unique shell-core structure with intimate contact inter-doping nanointerface. Moreover, the photocatalytic mechanism was discussed in detail. This work might provide a guideline in the design and construction of high-performance catalysts with well-defined nanointerface for various applications.

The hydrophobic ionic liquids/water two-phase system was developed to prepare CuO nano particles. The catalytic activity of the synthesized CuO was investigated by photodegradation of 4-nitrophenol (4-NP) in the presence of H2O2 under visible light irradiation. The optical properties of the synthesized CuO were characterized by ultraviolet–visible (UV–Vis) diffuse reflectance spectroscopy (DRS). Experimental results indicated that the band gap energy (Eg), conduction band edge potential (ECB) and valence band edge potential (EVB) of the synthesized CuO were 1.37 eV, 0.625 eV and 1.995 eV, respectively. A degradation efficiency of 4-NP (4.8 mmol L−1) as high as 95.3% could be achieved under the conditions of pH 6.0, 0.48 g L−1 of CuO dosage, 1.4% of H2O2 dosage and 90 min of degradation time. The synthesized CuO exhibited poor catalytic activity under alkaline conditions due to the disassociation of 4-NP, which elevated the repulsion between CuO and the 4-NP anions. The synthesized CuO nano particles exhibited higher catalytic activity compared with the catalysts reported in literature. Furthermore, the synthesized CuO nano particles could be reused at least six times without decreasing their catalytic activity. Compared with the traditional hydrothermal method, mild operating conditions and time saving are the advantages of the developed method for the preparation of CuO.

The sluggish reaction kinetics at the oxygen cathode is one of the important issues hindering the commercialization of the metal-air batteries. Although the noble metal can be used as the high-efficiency electrocatalyst to solve the problems to some extent, the high cost and scarcity of these noble-metal catalysts have limited their application in electrocatalysis. In this review, we discussed the mechanisms of the ORR and OER, and proposed the principles for the bifunctional electrocatalysts firstly, and then the state-of-the-art bifunctional catalysts, including carbon-based materials and transition-metal-based materials. On the basis of that, the self-supporting 3D noble-metal-free bifunctional ORR/OER catalysts were also discussed. Finally, the perspectives for the bifunctional electrocatalysts were discussed.

Defect-engineering in transition-metal-doped carbon-based catalyst plays an essential role for improving the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) performance. Herein, we report a ball-milling induced defect assisted with ZnCl2 strategy for fabricating defect-rich iron/nitrogen co-doped graphene-based materials (Fe-N-G). The substantial mechanical shear forces and the constant corrosion to the carbon matrix by ZnCl2 lead to the creation of abundant defects in graphene-based materials, which facilitates doping for heteroatoms. The defect-rich Fe-N-G catalyst with abundant Fe-Nx active sites displays excellent ORR performance. For OER, the over potential for Fe-N-G outperforms that of RuO2 in 1 M KOH at 10 mA cm−2. The Density Functional Theory calculations unravel that the impressive OER performance is attributable to the introduction of abundant defects. Additionally, the liquid and all-solid-state zinc-air batteries equipped with the prepared material as the air cathode demonstrate high power density, high specific capacity, and long charge–discharge stability. This work offers a practical method for manufacturing high-performance electrocatalysts for environmental and energy-related fields.

Clinical investigations to date have proposed the possibility that exposure to anesthetics is associated with neurodevelopmental deficits. Sevoflurane is the most commonly used general anesthetic in pediatric patients. Animal studies have demonstrated that multiple exposures to sevoflurane during the postnatal period resulted in neuropathological brain changes and long-term cognitive deficits.However, the underlying mechanisms remain to be clarified. In this study, methylated RNA immunoprecipitation sequencing (MeRIP-Seq) was performed to acquire genome-wide profiling of RNA N6-methyladenosine (m6A) in the prefrontal cortex of infant rhesus macaques. The macaques in the sevoflurane group had more m6A peaks than the macaques in the control group (p≤0.05). After sevoflurane treatment, the mRNA levels of YT521-B homology domain family 1 (YTHDF1) and YT521-B homology domain family 3 (YTHDF3) were decreased, and sevoflurane anesthesia dynamically regulated RNA m6A methylation. Gene ontology (GO) analysis revealed that after sevoflurane exposure, genes with increased methylation of m6A sites were enriched in some physiological processes relevant to neurodevelopment, mainly focused on synaptic plasticity. The female macaques had 18 hypermethylated genes. The males had 35 hypermethylated genes, and some physiological processes related to the regulation of synaptic structure were enriched. Rhesus macaques are genetically closer to human beings. Our findings can help in the study of the mechanism of sevoflurane-relevant neurodevelopmental deficits at the posttranscriptional level and can provide new insights into potential clinical preventions and interventions for the neurotoxicity of neonatal anesthesia exposure.

Summary Hydrogen has a remarkably flexible chemistry in oxides. We show that the introduction of H into simple TiO2 leads to greatly enhanced photocatalytic properties, and specifically yields a 60 times enhancement of photocatalytic hydrogen evolution activity over commercial rutile. The hydrogenated TiO2 (H-TiO2) is synthesized by a new one-step wet-chemistry approach yielding switchable defect via controlled annealing. As-prepared H-TiO2 has Ti-H bonds in the lattice from replacement of oxygen by hydrogen atoms. The Ti-H bonds are converted to oxygen vacancies by loss of H2O with Ar annealing. Oppositely, Ti-H defects are healed by Ti-O with O2 annealing. The strongly enhanced photocatalytic activity is associated with increased visible light absorption and effective separation of photogenerated carriers. This work provides a new and powerful approach for the preparation of hydrogenated titanium dioxide with switchable defect control, and striking improvement of photocatalytic activity.

The design of highly efficient noble-metal-free catalysts for fast hydrogenation of phenol to cyclohexanol is of great significance and quite challenging. Nickel-based Ni@C-T catalysts derived from Ni-MOF-74 with different pyrolysis temperatures (T) were prepared and characterized by various methods. The effect of T on the selective hydrogenation of phenol over Ni@C-T was studied. The results showed that metallic Ni is identified as the main activity site for the hydrogenation of phenol and the active metallic Ni was formed at the pyrolysis temperature higher than 400 °C. Ni@C-400 exhibited the best performance under mild conditions. The conversion of phenol reached 100% with a cyclohexanol selectivity of 100% under the reaction conditions of a temperature of 120 °C, a H2 pressure of 2.0 MPa and a time of 2 h, which are more excellent than those of reported catalysts. Furthermore, Ni@C-400 showed perfect reusability. The excellent catalytic performance of Ni@C-400 was associated with its high surface area and better dispersion of active sites due to the metal–organic framework.

Aqueous Zn-ion batteries (AZIBs) are promising candidates for large-scale energy storage owing to their intrinsic safety and low cost. However, the formation of Zn dendrite caused by uneven deposition on Zn anode severely impedes the lifespan of AZIBs. Herein, we propose a green and low-cost additive, nettle extract (NE), to guide the uniform Zn deposition via in-situ engineered zincophilic sites. We show by both experiments and theoretical calculations that the zincophilic molecules contained in NE can adsorb on Zn anode surface to offer more effective sites for Zn nucleation, thus effectively suppressing the dendrite growth. Significantly, the Zn||Zn symmetric cell with NE can stably cycle over 2200 h at 5 mA cm−2 with 5 mAh cm−2 capacity. A Zn||polyaniline/carbon felt full cell also gains 84.9% capacity retention after 1500 cycles. Our strategy of engineering zincophilic sites on Zn anode via plant extracts additives ushers in new possibilities to develop dendrite-free Zn anode.

In pursuit of environmental friendliness and high economic efficiency, renewable energy-driven selective acetylene semihydrogenation under ambient conditions is urgently requisite but remain a grand challenge. Herein, we explore single-atom nickel (Ni) dispersed N-doped carbon (SA-Ni-NC) as novel electrocatalysts for catalyzing selective acetylene semihydrogenation. In-situ electrochemical Raman and theoretical investigations reveal that weak π-adsorption of ethylene on individual Ni sites in SA-Ni-NC facilitates its desorption and thus avoids its overhydrogenation. Eventually, under pure acetylene flow, SA-Ni-NC exhibits a high ethylene Faradaic efficiency (FEethylene) of 91.3 %, and a large current density of −92.2 mA cm−2 at −0.6 V vs. reversible hydrogen electrode (RHE). Even in crude ethylene stream containing 1 % acetylene impurities (1×104 ppm), SA-Ni-NC still manifest a high acetylene conversion of 97.4 % with a large space velocity (SV) of 2.4×104 mL gcat–1 h–1 and a high turnover frequency (TOF) of 22.9 h−1 for each Ni atom.

Three previously undescribed compounds including two ergosterols, diaporthins A and B (1 and 2), and a pyrrolidinone derivative, (±)-diaporthin C (3), together with three known compounds 4‒6, were isolated from cultures of kiwi-associated fungus Diaporthe phragmitis. The racemic 3 was further separated into pure enantiomers. Their structures with absolute configurations were elucidated by means of spectroscopic analysis, as well as single crystal X-ray diffraction analysis and electronic circular dichroism (ECD) calculations. Compounds 5 and 6 showed antibacterial activity against Pseudomonas syringae pv. actinidae with MIC values of 25 and 6.25 μg/mL, respectively.

CYP76AH1 is the key enzyme in the biosynthesis pathway of tanshinones in Salvia miltiorrhiza, which are famous natural products with activities against various heart diseases and others. CYP76AH1 is a membrane-associated typical plant class II cytochrome P450 enzyme and its catalytic mechanism has not to be clearly elucidated. Structural determination of eukaryotic P450 enzymes is extremely challenging. Recently, we solved the crystal structures of CYP76AH1 and CYP76AH1 in complex with its natural substrate miltiradiene. The structure of CYP76AH1 complexed with miltiradiene is the first plant cytochrome P450 structure in complex with natural substrate. The studies revealed a unique array pattern of amino acid residues, which may play an important role in orienting and stabilizing the substrate for catalysis. This work would provide structural insights into CYP76AH1 and related P450s and the basis to efficiently improve tanshinone production by synthetic biology techniques.

Antimicrobial resistance in Gram-negative bacteria has become one of the leading causes of morbidity and mortality and a serious worldwide public health concern due to the fact that Gram-negative bacteria have an additional outer membrane protecting them from an unwanted compound invading. It is still very difficult for antimicrobials to reach intracellular targets and very challenging to treat Gram-negative bacteria with the current strategies. Here, we found that (o-(bromomethyl)phenyl)boronic acid was incorporated into poly((2-N,N-diethyl)aminoethyl acrylate) (PDEA), forming a copolymer (poly(o-Bn-DEA)) having both phenylboronic acid (B) and ((2-N,N-diethyl)amino) (DEA) units. Poly(o-Bn-DEA) exhibits very strong intramolecular B-N coordination, which could highly promote the covalent binding of phenylboronic acid with lipopolysaccharide (LPS) on the outer membrane of E. coli and lodge poly(o-Bn-DEA) on the LPS layer on the surface of E. coli. Meanwhile, the strong electrostatic interaction between poly(o-Bn-DEA) and the negatively charged lipid preferred tugging the poly(o-Bn-DEA) into the lipid bilayer of E. coli. The combating interactions between covalent binding and electrostatic interaction form a tug-of-war action, which could trigger the lysis of the outer membrane, thereby killing Gram-negative E. coli effectively without detectable resistance.

Background: Trimethylamine-N-oxide (TMAO) is an intestinal metabolic toxin, which is produced by gut flora via metabolizing high-choline foods. TMAO is known to increase the risk of atherosclerosis and cardiovascular events in chronic kidney disease (CKD) patients. Objectives: The objective of this study was to explore the role and mechanism of TMAO aggravating kidney injury. Method: We used the five-sixths nephrectomy (5/6 Nx)-induced CKD rats to investigate whether TMAO could aggravate kidney damage and its possible mechanisms. Six weeks after the operation, the two groups of 5/6 Nx rats were subjected to intraperitoneal injection with 2.5% glucose peritoneal dialysis fluid (2.5% PDF) and 2.5% PDF plus TMAO 20 mg/kg/day. Results: In this study, we provided evidence showing TMAO significantly aggravated renal failure as well as inflammatory cell infiltration and in five-sixths nephrectomy-induced CKD rats. We found that TMAO could upregulate inflammatory factors including MCP-1, TNF-α, IL-6, IL-1β, and IL-18 by activating p38 phosphorylation and upregulation of human antigen R. TMAO could aggravate oxidative stress by upregulating NOX4 and downregulating SOD. The result also confirmed that TMAO promoted NLRP3 inflammasome formation as well as cleaved caspase-1 and IL-1β activation in the kidney tissue. Conclusions: Taken together, the present study validates TMAO as a pro-inflammatory factor that causes renal inflammatory injury and renal function impairment. Inhibition of TMAO synthesis or promoting its clearance may be a potential therapeutic approach of CKD in the future.

Purposefully designing the well-defined catalysts for the selective electroreduction of CO2 to C2 H4 is an extremely important but challenging work. In this work, three crystalline trinuclear copper clusters (Cu3 -X, X=Cl- , Br- , NO3- ) have been designed, containing three active Cu sites with the identical coordination environment and appropriate spatial distance, delivering high selectivity for the electrocatalytic reduction of CO2 to C2 H4 . The highest faradaic efficiency of Cu3 -X for CO2 -to-C2 H4 conversion can be adjusted from 31.90 % to 55.01 % by simply replacing the counter anions (NO3- , Cl- , Br- ). The DFT calculation results verify that Cu3 -X can facilitate the C-C coupling of identical *CHO intermediates, subsequently forming molecular symmetrical C2 H4 product. This work provides an important molecular model system and a new design perspective for electroreduction of CO2 to C2 products with symmetrical molecular structure.

Background: Santacruzamate A (SCA) is a natural product isolated from a marine cyanobacterium. Activity test results revealed that SCA is a highly potent HDAC2 inhibitor with an IC50 value of 0.112 nM. The IC50 of SCA in inhibiting cancer cell proliferation is 28.3 μM and 1.3μM on HCT116 and HuT-78 cells, respectively. Objective: To develop HDAC inhibitors with improved activity, SCA analogs were synthesized for the structure-activity relationship (SAR) studies. Method: Various substituted groups were introduced into the zinc binging group, linker, and cap regions of SCA by various chemical synthetic methods. Result: Compared with SCA, the derivatives of SCA did not exhibit improved HDAC2 inhibitory activity. Nevertheless, several molecules such as III-32, III-33, IV-4b, and IV-11 showed improved activity in inhibiting cell proliferation on HCT116 and HuT-78 cells. Conclusion: Collectively, a potent HDAC2 inhibitor SCA was discovered as a lead compound for further development of selective HDAC inhibitors.

As two pivotal functional segments, triazine and porphyrin can be coupled to form a highly cross-linked conjugated polymer. Although the obtained conjugated polymers are almost insoluble in most so...

BackgroundPolygonatum kingianumColl. et Hemsl. is an important plant in Traditional Chinese Medicine. The extracts from its tubers are rich in polysaccharides and other metabolites such as saponins. It is a well-known concept that growing medicinal plants in semi-arid (or drought stress) increases their natural compounds concentrations. This study was conducted to explore the morpho-physiological responses ofP. kingianumplants and transcriptomic signatures ofP. kingianumtubers exposed to mild, moderate, and severe drought and rewatering.ResultsThe stress effects on the morpho-physiological parameters were dependent on the intensity of the drought stress. The leaf area, relative water content, chlorophyll content, and shoot fresh weight decreased whereas electrolyte leakage increased with increase in drought stress intensity. A total of 53,081 unigenes were obtained; 59% of which were annotated. We observed that 1352 and 350 core genes were differentially expressed in drought and rewatering, respectively. Drought stress driven differentially expressed genes (DEGs) were enriched in phenylpropanoid biosynthesis, flavonoid biosynthesis, starch and sucrose metabolism, and stilbenoid diarylheptanoid and gingerol biosynthesis, and carotenoid biosynthesis pathways. Pathways such as plant-pathogen interaction and galactose metabolism were differentially regulated between severe drought and rewatering. Drought reduced the expression of lignin, gingerol, and flavonoid biosynthesis related genes and rewatering recovered the tubers from stress by increasing the expression of the genes. Increased expression of carotenoid biosynthesis pathway related genes under drought suggested their important role in stress endurance. An increase in starch and sucrose biosynthesis was evident from transcriptomic changes under drought stress. Rewatering recovered the drought affected tubers as evident from the contrasting expression profiles of genes related to these pathways.P. kingianumtuber experiences an increased biosynthesis of sucrose, starch, and carotenoid under drought stress. Drought decreases the flavonoids, phenylpropanoids, gingerol, and lignin biosynthesis. These changes can be reversed by rewatering theP. kingianumplants.ConclusionsThese results provide a transcriptome resource forP. kingianumand expands the knowledge on the effect of drought and rewatering on important pathways. This study also provides a large number of candidate genes that could be manipulated for drought stress tolerance and managing the polysaccharide and secondary metabolites’ contents inP. kingianum.

Electrocatalytic acetylene semihydrogenation is a promising alternative to thermocatalytic acetylene hydrogenation due to its environmental benignity and economic efficiency, but its performance is far below that of the thermocatalytic reaction because of strong competition from side reactions, including hydrogen evolution, overhydrogenation and carbon–carbon coupling reactions. We develop N–heterocyclic carbene–metal complexes, with electron–rich metal centers owing to the strongly σ–donating N–heterocyclic carbene ligands, as electrocatalysts for selective acetylene semihydrogenation. Experimental and theoretical investigations reveal that the copper sites in N–heterocyclic carbene–copper facilitate the absorption of electrophilic acetylene and the desorption of nucleophilic ethylene, ultimately suppressing the side reactions during electrocatalytic acetylene semihydrogenation, and exhibit superior semihydrogenation performance, with faradaic efficiencies of ≥98 % under pure acetylene flow. Even in a crude ethylene feed containing 1 % acetylene (1 × 104 ppm), N–heterocyclic carbene–copper affords a specific selectivity of >99 % during a 100–h stability test, continuous ethylene production with only ~30 ppm acetylene, a large space velocity of up to 9.6 × 105 mL·gcat−1·h−1, and a turnover frequency of 2.1 × 10−2 s−1, dramatically outperforming currently reported thermocatalysts., This study explores N–heterocyclic carbene copper complexes toward selective electrocatalytic reduction of acetylene to ethylene. The electron–rich copper sites were found to facilitate acetylene adsorption and ethylene desorption and achieved high activity and selectivity for ethylene production.

Tailoring non-flammable phosphate-based electrolytes with high safety and good Li reversibility are in urgent demand for practical lithium metal batteries. However, phosphate-ester exhibits a poor compatibility with active Li surface and the key to solve this challenge is to build a sustainable solid-electrolyte interphase. Herein, dual-layer crystalline/polymeric solid electrolyte interphase (SEI) is designed in phosphate ester/ether mixed electrolyte utilizing lithium difluoro(oxalato)borate (LiDFOB) as main salt. The coordinated ether in Li solvation sheath will be reduced in Li metal surface, forming alkoxides residue in the early cycling stage, which will further react with DFOB− to form an outer Li2O, inner amorphous polyether SEI layer. Consequently, the flame-retardant electrolyte exhibits a low self-extinguishing time of 6.10 s g−1 and a satisfied Li reversibility of 98.31% in NCM/Cu configuration. The coin-type limited-excess Li/LiNi0.8Mn0.1Co0.1O2 (NCM811) full cell with negative to positive electrode capacity ratio (N/P) of 1.92 can cycle for more than 140 cycles. Meanwhile, a pouch cell with ∼0.2 Ah capacity, low N/P ratio of ∼2.22 shows a good capacity retention of 87.9% after 60 cycles without Li exhaustion.

Binder-free NiFe-based electrocatalyst with aligned pore channels has been prepared by freeze casting and served as a bifunctional catalytic electrode for oxygen and hydrogen evolution reaction (OER and HER). The synergistic effects between Ni and Fe result in the high electrocatalytic performance of porous NiFe electrodes. In 1.0 M KOH, porous Ni7Fe3 attains 100 mA cm−2 at an overpotential of 388 mV with a Tafel slope of 35.8 mV dec−1 for OER, and porous Ni9Fe1 exhibits a low overpotential of 347 mV at 100 mA cm−2 with a Tafel slope of 121.0 mV dec−1 for HER. The Ni9Fe1//Ni9Fe1 requires a low cell voltage of 1.69 V to deliver 10 mA cm−2 current density for overall water splitting. The excellent durability at a high current density of porous NiFe electrodes has been confirmed during OER, HER and overall water splitting. The fine electrocatalytic performances of the porous NiFe-based electrodes owing to the three-dimensionally well-connected scaffolds, aligned pore channels, and bimetallic synergy, offering excellent charge/ion transfer efficiency and sizeable active surface area. Freeze casting can be applied to design and synthesize various three-dimensionally porous non-precious metal-based electrocatalysts with controllable multiphase for energy conversion and storage.

Due to the antioxidant properties of lignin, it has been demonstrated as an active substance for treating oxidation-related and inflammatory diseases. However, how the structural properties of lignin affect its biological activities is still ambiguous. In this study, Kraft lignin from wheat straw (KL-A) was used as the raw material to fractionate into three fractions (e.g., KL-B, KL-C, and KL-D) with different molecular weight by ultrafiltration, which possessed different physicochemical properties. The biocompatibility, in vivo and in vitro scavenging abilities for reactive oxygen species (ROS), and anti-apoptotic abilities of the lignin fractions were evaluated using SW1353 chondrocyte cell lines and were quantitatively fitted to their physicochemical properties. The results showed that lignin fractions with lower molecular weights, lower G/S ratios, and higher non-condensed phenolic OH contents endowed lignin with stronger ROS scavenging ability in vivo and in vitro, but was accompanied by increased cytotoxicity to cells. The half maximal inhibitory concentration (IC50) of KL-A, KL-B, KL-C, and KL-D were separately determined as 44.02, 33.43, 32.41, and 18.40 μg/mL. Furthermore, KL-D, with the lowest molecular weight and highest number of functional groups, showed the best antioxidant ability, while it performed poorly in inhibiting cellular apoptosis of chondrocytes. Compared to KL-D, KL-C with inverse structural properties, performed better in anti-apoptosis of SW1353 cells, which is the optimum lignin as promising active substances to be applied in the treatment of osteoarthritis in biomedical engineering.

In order to eliminate multiple coexisting pollutants in environmental wastewater, a magnetic three-dimensional hierarchical porous flower-like N, Co-doped graphitic carbon nano-polyhedra decorated NiCo-layered double oxides (N-Co@C/NiCo-LDOs) adsorption material was synthesized, which consisted of two-dimensional LDOs nanosheets with functionalized surfaces (N, Co-doped graphitic carbon loaded on both sides of NiCo-LDOs nanosheets). The adsorption properties of N-Co@C/NiCo-LDOs for five types of typical pollutants (cationic dyes: rhodamine b, methylene blue; pesticides: ethofenprox, bifenthrin; anionic dyes: methyl orange, congo red; inorganic cations: Cr2+, Cd2+, Pb2+, Zn2+, inorganic anions: Cr2O72−, AsO33−) were investigated systematically in single and coexisting systems. Combined with the results of FTIR and zeta potential, the adsorption mechanism was discussed. By virtue of its hierarchical porous architecture and the combined effect of functionalized surfaces and LODs supporter, the as-prepared N-Co@C/NiCo-LDOs demonstrates excellent adsorption performance towards five types of typical pollutants with fast adsorption rate, high adsorption capacity and good co-adsorption performance. More importantly, the N-Co@C/NiCo-LDOs showed satisfactory removal efficiency, stability and reusability in model wastewater. The broad-spectrum, rapid, easily separable, and reusable adsorption properties make N-Co@C/NiCo-LDOs promising for highly efficient wastewater treatments. This work also provides a feasible way for the preparation of adsorption materials for the treatment of complex wastewater systems.

Signaling pathway-driven target gene transcription is critical for fate determination of embryonic stem cells (ESCs), but enhancer-dependent transcriptional regulation in these processes remains poorly understood. Here, we report enhancer architecture-dependent multilayered transcriptional regulation at the Halr1–Hoxa1 locus that orchestrates retinoic acid (RA) signaling-induced early lineage differentiation of ESCs. We show that both homeobox A1 (Hoxa1) and Hoxa adjacent long non-coding RNA 1 (Halr1) are identified as direct downstream targets of RA signaling and regulated by RARA/RXRA via RA response elements (RAREs). Chromosome conformation capture-based screens indicate that RA signaling promotes enhancer interactions essential for Hoxa1 and Halr1 expression and mesendoderm differentiation of ESCs. Furthermore, the results also show that HOXA1 promotes expression of Halr1 through binding to enhancer; conversely, loss of Halr1 enhances interaction between Hoxa1 chromatin and four distal enhancers but weakens interaction with chromatin inside the HoxA cluster, leading to RA signaling-induced Hoxa1 overactivation and enhanced endoderm differentiation. These findings reveal complex transcriptional regulation involving synergistic regulation by enhancers, transcription factors and lncRNA. This work provides new insight into intrinsic molecular mechanisms underlying ESC fate determination during RA signaling-induced early differentiation., Graphical Abstract Graphical AbstractEnhancer architecture-dependent multilayered transcriptional regulation at the Halr1–Hoxa1 locus that orchestrates RA signaling-induced early lineage differentiation of ESCs.

In this paper, the intermetallic compound (IMC) growth behaviors of Sn/Cu and Sn–0.6SiC/Cu solder under isothermal aging (50, 100, 150, 200 and 250 h) and thermal cycling (300, 600, 900, 1200 and 1500 cycles) were studied. The results manifested that the IMC layer got thicker in Sn/Cu solder and Sn–0.6SiC/Cu solder as the aging time or thermal cycles increased, but the IMC thickness of Sn solder incorporated with silicon carbide nanowires (SiC NWs) was smaller than that of Sn solder in the same condition. According to the adsorption theory, SiC NWs would adsorb on the IMC grains and then reduce the surface tension of IMC, which made for the suppression of IMC growth. Also, SiC NWs could nail at grain boundaries and then prohibit the further growth of IMC grains. Thus, doping 0.6 wt% SiC NWs could reduce the size of IMC grains and decrease the diffusion coefficient of IMC growth, which led to prohibiting the interfacial IMC growth at solder/substrate under isothermal aging. During thermal cycling process, SiC NWs addition was beneficial to decrease the rate of IMC growth at the interface of Sn/Cu solder. Moreover, adding SiC NWs into Sn solder could improve the reliability of solder joints in that there were less cracks formed at IMC layer in Sn–SiC/Cu solder.

Metal-organic frameworks (MOFs), serving as precursors or templated to construct nanomaterials, which have gained great attentions in the field of electrocatalysis. However, their applications still remain some challenges due to poor conductivity and easy agglomeration. In this work, the MOFs-derived NiCo2S4@NiCo2O4 deposited on reduced Graphene Oxide (rGO) surface is designed by using a facile hydrothermal procedure. Attribute to the enlarged active surface area of the nanostructure and the strong synergistic effect between NiCo2S4 and NiCo2O4, as well as the excellent conductivity of rGO. The NiCo2S4@NiCo2O4-rGO catalyst displays ultrahigh hydrogen evolution reaction (HER) property and excellent stability, only need an overpotential of η10 = 95 mV to attain 10 mA cm−2 and deliver a small Tafel slope of b = 52 mV dec−1 in 1 M KOH. This work can provide a window to construct and develop new noble metal-free HER catalysts base on Ni-MOFs served as precursors.

A novel type of functional graphene oxide nanosheets (GNs) modified with β-cyclodextrins (β-CDs) have been developed by coating dopamine-functionalized cyclodextrin (DACD) molecules on GNs for removing Bisphenol A (BPA) molecules from water. The DACD molecules with both β-CD groups for achieving adsorption property and dopamine (DA) groups for achieving adhesion property are synthesized by grafting DA onto carboxymethyl-β-cyclodextrin (CmβCD). The proposed DACD molecules can be firmly coated on the surfaces of various inorganic and organic substrates. Due to the large specific surface area of GNs, DACD-coated GNs (DACD@GNs) are proposed for efficient adsorption separation of BPA molecules from water. Due to the host-gust complexation between the BPA molecules in water and β-CDs on DACD@GNs, the fabricated DACD@GNs exhibit excellent adsorption performances. The adsorption kinetics can be explained via the pseudo-second-order model effectively. The experimental adsorption capacity of DACD@GNs is 11.29 mg·g−1 for BPA. Furthermore, after the adsorption process, the DACD@GNs can be easily separated from aqueous solutions via vacuum filtration with porous membranes, and then regenerated by simply washing with ethanol. The proposed strategy in this study can be used for effectively functionalizing the surfaces of various substrates with functional β-CDs, which is highly promising in applications in the field of adsorption separations, especially water treatments.

RNA methylations contribute to a wide range of cellular functions. Cellular RNAs are usually methylated by protein methyltransferases using S-adenosyl-l-methionine (SAM) as a cofactor. Here we report the in vitro selection of a 33-nucleotide SAM-dependent methyltransferase ribozyme RNA from a randomized sequence. Detection and mapping of the methyl group on the RNA demonstrates site-specific methylation of the N7 position of guanine by SAM. The ribozyme is active over a wide range of pH and temperatures and is robust compared to protein enzymes. The ribozyme structures in the presence and absence of SAM show a dramatic local conformational change associated with cofactor binding. The ribozyme motif was found to be distributed in nature, and candidate sequences were shown to be active in vitro. The discovery of this ribozyme that uses the cofactor SAM to specifically methylate RNA opens up the possibility that methyltransferase ribozymes may contribute to cellular RNA methylation. Ribozymes that use the cellular cofactor S-adenosyl-l-methionine to methylate RNA remained elusive. Now, such a ribozyme is reported by identifying natural sequences that are active in vitro; and crystal structures of the ribozyme with and without the cofactor are determined.

Bacterial chromosome replication is mainly catalyzed by DNA polymerase III, whose beta subunits enable rapid processive DNA replication. Enabled by the clamp-loading complex, the two beta subunits form a ring-like clamp around DNA and keep the polymerase sliding along. Given the essential role of β-clamp, its inhibitors have been explored for antibacterial purposes. Similarly, β-clamp is an ideal target for bacteriophages to shut off host DNA synthesis during host takeover. The Gp168 protein of phage Twort is such an example, which binds to the β-clamp of Staphylococcus aureus and prevents it from loading onto DNA causing replication arrest. Here, we report a cryo-EM structure of the clamp–Gp168 complex at 3.2-Å resolution. In the structure of the complex, the Gp168 dimer occupies the DNA sliding channel of β-clamp and blocks its loading onto DNA, which represents a new inhibitory mechanism against β-clamp function. Interestingly, the key residues responsible for this interaction on the β-clamp are well conserved among bacteria. We therefore demonstrate that Gp168 is potentially a cross-species β-clamp inhibitor, as it forms complex with the Bacillus subtilis β-clamp. Our findings reveal an alternative mechanism for bacteriophages to inhibit β-clamp and provide a new strategy to combat bacterial drug resistance.

A robust superhydrophobic perfluoropolysiloxane and self-doped polyaniline/epoxy resin composite coating (EPAN-RA-POS) was prepared. The structure is composed of the internal self-doped polyaniline...

Background Soleris®E. coli is an automated, growth-based method for detection and semi-quantitative determination of Escherichia coli in foods. The method can be used in dilute-to-specification (threshold) or presence/absence modes. Objective The objective of the study was to validate four modifications to the method: (1) a change in the vial detection window plug composition from agar to agarose to improve plug consistency and robustness, (2) a change in pre-enrichment incubation time for presence/absence testing from 6 h to 18–24 h, (3) a change in vial incubation temperature from 44.5 to 43.5°C, and (4) incorporation of a simple direct-from-vial confirmation test as an alternative to traditional procedures. Methods Elements of the study included inclusivity/exclusivity testing, matrix testing in comparison to the ISO 7251:2005 reference method, reagent stability/lot-to-lot consistency testing, and an independent laboratory study. Results In inclusivity testing, all 55 Escherichia coli strains tested produced positive results. In exclusivity testing, 30 of 31 strains of other bacterial species produced negative results, the sole exception being a strain of Enterobacter cloacae. In internal and independent laboratory matrix testing of mozzarella cheese, condensed milk, pasteurized liquid egg, and frozen green beans, results showed no significant differences in performance of the Soleris and reference methods with two exceptions, one in which the Soleris method produced more positive results, and one in which the reference method produced more positive results. Conclusion Performance characteristics of the modified Soleris E. coli method are consistent with those of the original validated method. Highlights The Soleris E. coli method offers improvements in ease of use and reagent robustness.

Drought stress is a severe environmental factor that greatly restricts plant distribution and crop production. Transgenic breeding offers new opportunities for developing drought-resistant varieties. The WRKY transcription factors have been reported to be involved in various plant physiological and biochemical processes. In this study, we report the impact of TaWRKY46 on abiotic tolerance in wheat (Triticum aestivum L.). The transcription levels of the TaWRKY46 gene were differentially regulated by diverse abiotic stresses and hormone treatments, including PEG-induced stress (20% polyethylene glycol 6000), cold (4 °C), salt (100 mM NaCl), abscisic acid (100 μM ABA) and hydrogen peroxide (10 mM H2O2). The TaWRKY46-GFP fusion protein was localized to the nucleus of wheat protoplast. The N-terminal of TaWRKY46 showed transcriptional activation activity. Overexpression of TaWRKY46 in wheat resulted in enhanced drought stress tolerance. TaWRKY46-overexpressing plants exhibited increase survival rate, soluble sugar, proline and superoxide dismutase (SOD), as well as higher activities of catalase (CAT) and peroxidase (POD), but lower contents of malondialdehyde (MDA) and H2O2 content. Taken together, our results indicate that TaWRKY46 functions as a positive factor under drought stress by regulating the osmotic balance and ROS scavenging.

Pyridine-based ring systems are one of the most extensively used heterocycles in the field of drug design, primarily due to their profound effect on pharmacological activity, which has led to the discovery of numerous broad-spectrum therapeutic agents. In the US FDA database, there are 95 approved pharmaceuticals that stem from pyridine or dihydropyridine, including isoniazid and ethionamide (tuberculosis), delavirdine (HIV/AIDS), abiraterone acetate (prostate cancer), tacrine (Alzheimer’s), ciclopirox (ringworm and athlete’s foot), crizotinib (cancer), nifedipine (Raynaud’s syndrome and premature birth), piroxicam (NSAID for arthritis), nilvadipine (hypertension), roflumilast (COPD), pyridostigmine (myasthenia gravis), and many more. Their remarkable therapeutic applications have encouraged researchers to prepare a larger number of biologically active compounds decorated with pyridine or dihydropyridine, expandeing the scope of finding a cure for other ailments. It is thus anticipated that myriad new pharmaceuticals containing the two heterocycles will be available in the forthcoming decade. This review examines the prospects of highly potent bioactive molecules to emphasize the advantages of using pyridine and dihydropyridine in drug design. We cover the most recent developments from 2010 to date, highlighting the ever-expanding role of both scaffolds in the field of medicinal chemistry and drug development.

Hydrogen (H2) generation from formic acid (FA) decomposition is a promising route in practical application of hydrogen energy. As a promising H2 supplier, besides the advantage of high H2 content and excellent stability, FA can also be used as a mild reducing agent. Herein, an in-situ prepared NiAuPd nanoparticles (NPs) supported on amine-functionalized carbon nanotubes (NiAuPd/NH2-CNTs) with FA as the reducing agent is successfully developed at room temperature. The as-prepared NiAuPd/NH2-CNTs are directly used for the catalytic decomposition of FA, exhibiting excellent activity and 100% H2 selectivity with the initial turnover frequency (TOFinitial) value of 699.1 and 3006.1 mol H2 mol Pd-1 h-1 at 303 and 333 K, respectively. Moreover, the additive sodium formate (SF) can further facilitate the reduction process and enhance the catalytic performance, with the TOFinitial value of 4391.1 mol H2 mol Pd-1 h-1 at 333 K, which are comparable to most of the reported heterogeneous catalysts with the complicated post-treatment. The excellent catalytic performance of NiAuPd/NH2-CNTs is mainly attributed to the high dispersion of NPs and the boost effect of -NH2 group on O–H cleavage. This work provides a feasible strategy to design in-situ prepared catalysts for the efficient high-quality H2 generation from FA for fuel cells application.

Aluminum nitride (AlN) ceramic is a material with many excellent properties, such as high thermal conductivity and outstanding electrical insulation, but the required raw powders are easily hydrolyzed that affects the performance after sintering. Therefore, surface modification of AlN powder is essential. In this study, the raw AlN powders were treated in an ethanol with silicic acid (H2SiO3) by heating and stirring at 80 °C. The treated powders will not be hydrolyzed under high temperature and stirring, which was confirmed by pH measurement (pH), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and Transmission Electron Microscope (TEM) etc. methods. The XRD spectra proves that the characteristic crystalline peaks of the treated AlN powders after impregnating warm aqueous solution over twenty days are still the same as those of the raw AlN powders. The pH value of the suspension with treated AlN powders remains constant at 7.0–8.0 in 80 °C/90 °C water for 72 h. FTIR and TEM analysis shows that a 3–18 nm protective layer of Si–O–Si wrapped on the surface of the AlN powders. These results directly indicate that the AlN powders treated with H2SiO3 have good hydrolysis resistance. Moreover, the relative density and thermal conductivity of the ceramics sintered by the treated AlN powders can reach 97.21% and 144.505 w/(m· K), respectively.

Quantification of hippuric acid and methylhippuric acid in human urine matrices provides information on the toluene and xylene exposure conditions. High performance liquid chromatography coupled with UV detection is the preferable technique for hippuric acid and methylhippuric acid detection in human urine. This study was conducted to present analytical techniques developed for monitoring of hippuric acid and methylhippuric acid in human urine matrices during 2016–2021.

Fourteen alkaloids of diverse carbon skeletons, including a new compound 2R-4-(5′-methyl-pyrazin)-2-yl-but-3-ene-1,2-diol (1) and a new natural product methyl 2-(4-hydroxyphenyl)acetyl glycinate (3), were isolated from the ethanol extract of Acorus calamus Linn. rhizomes. Their structures were determined based on extensive spectroscopic analyses and comparing of the literature data. Compounds 1–5 were evaluated for their in vitro PPARα, PPARγ, and glucokinase-activating activities, and neotatarine (4) exhibited significant PPARα and PPARγ activating activities at 10−6 mol/L, and it also exhibited significant glucokinase activating activities at 10-5 mol/L. Furthermore, molecular docking of compound 4 bound with PPARα, PPARγ, and GK was carried out to investigate some possible structural insights into the potential binding patterns.

Nitrogen-doped transition metal materials display promising potential as bifunctional electrocatalysts for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). Herein, Fe/N co-doped three-dimensional (3D) porous graphene (FeN-3D-PG) is prepared via a template method using sodium alginate as the carbon source and low polymerization degree melamine resin as the nitrogen source. The low polymerization degree melamine resin can form complexes with Fe3+ in the aqueous solution and further forms high density Fe-Nx active sites during pyrolysis. Meanwhile, the formed 3D porous structure efficiently promotes the uniform distribution of Fe-Nx active sites. The FeN-3D-PG catalyst exhibits pH-independent ORR activity. For OER, the catalyst possesses a low over potential (370 mV at 10 mA cm−2) in alkaline electrolyte. The Zn-air batteries (ZABs) using FeN-3D-PG as cathode exhibits a power density up to 212 mW cm−2, a high specific capacity of 651 mAh g−1, and the charge-discharge stability of 80 h. This work provides new sight to transition metal materials based ZABs with excellent performance.

Developing renewable energy technology is an effective way to address the global warming and air pollution problems derived from depleting fossil fuels. Due to the high theoretical capacity (3860 mAh g−1) and low electrochemical potential of lithium metal anode, lithium metal batteries (LMBs) have attracted tremendous research attention with the scalable application and vigorous deployment of electric vehicles. Unfortunately, the further commercialization of Li metal anode is hindered by the random growth of Li dendrites during the lithium plating/stripping processes, leading to the continuous consumption of active Li and the puncture on the separator. Just recently, Ma's group proposed a new approach to systematically investigate the relationship between functional groups and Li dendrite generation during the Li plating/stripping processes. The proposed new approach could be of an effective tool to gain new insights into functional groups in the electrolyte additives and Li dendrites formation, highly valuable for the rational structural design of highperformance Li metal electrode materials.

The value of catalytic dehydrogenation of aliphatics (CDA) in organic synthesis has remained largely underexplored. Known homogeneous CDA systems often require the use of sacrificial hydrogen acceptors (or oxidants), precious metal catalysts, and harsh reaction conditions, thus limiting most existing methods to dehydrogenation of non- or low-functionalized alkanes. Here we describe a visible-light-driven, dual-catalyst system consisting of inexpensive organophotoredox and base-metal catalysts for room-temperature, acceptorless-CDA (Al-CDA). Initiated by photoexited 2-chloroanthraquinone, the process involves H atom transfer (HAT) of aliphatics to form alkyl radicals, which then react with cobaloxime to produce olefins and H2. This operationally simple method enables direct dehydrogenation of readily available chemical feedstocks to diversely functionalized olefins. For example, we demonstrate, for the first time, the oxidant-free desaturation of thioethers and amides to alkenyl sulfides and enamides, respectively. Moreover, the system's exceptional site selectivity and functional group tolerance are illustrated by late-stage dehydrogenation and synthesis of 14 biologically relevant molecules and pharmaceutical ingredients. Mechanistic studies have revealed a dual HAT process and provided insights into the origin of reactivity and site selectivity.

BACKGROUND: Oxidized low-density lipoprotein (ox-LDL) could induce endothelial injury and played a vital role in the progression and development of atherosclerosis. This study aimed to investigate the role of Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) in ox-LDL-induced human umbilical vascular endothelial cells (HUVECs) injury and the potential mechanisms. METHODS: Cell proliferation and apoptosis were evaluated by Cell Counting Kit-8 (CCK-8) assay and flow cytometry assay, respectively. The levels of lactate dehydrogenase (LDH), reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO) were detected by corresponding detection kits, respectively. Quantitative real-time PCR (qRT-PCR) was conducted to measure the expression of OIP5-AS1 or microRNA-30c-5p (miR-30c-5p) in HUVECs. Binding between OIP5-AS1 and miR-30c-5p was predicted through bioinformatics analysis and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP). Western blot was used to analyze p-IκB, IκB, p-p65 and p65 levels. RESULTS: In HUVECs, exposure to ox-LDL led to a decrease in cell viability and an increase in LDH release and apoptosis with concomitant enhancement of oxidative stress, as evidenced by increased ROS and MDA generation, as well as decreased SOD activity and NO levels, while OIP5-AS1 knockdown or miR-30c-5p upregulation could rescue these effects above. Mechanically, OIP5-AS1 functioned as a sponge of miR-30c-5p. OIP5-AS1-induced injury and apoptosis, oxidative stress and activation of NF-κB pathway were reversed by miR-30c-5p in ox-LDL-treated HUVECs. CONCLUSION: OIP5-AS1 contributed to ox-LDL-treated HUVECs injury by activation of NF-κB pathway via miR-30c-5p.